Recent advances in molecular biology have provided a vast array of potential new bioactive agents. However, it has been estimated that 60% of new bioactive agents exhibit limited water solubility. Formulating poorly water soluble bioactive agents into suitable dosage forms poses a significant challenge due to difficulties in achieving adequate bioavailability of the bioactive agent in an aqueous biological system.
In principle, the bioavailability of poorly water-soluble bioactive agents can be improved by decreasing the particle size of the bioactive agent. Various methods of reducing particle size have been explored, including milling, high pressure homogenization, spray drying, lyophilization of solutions in water-organic solvent mixtures, and lyophilization of solutions in organic solvents. However, existing approaches for micronizing poorly water-soluble drugs have significant drawbacks. For example, many conventional approaches fail to provide precise control of particle size and/or particle size distribution. Other methods require the use of organic solvents that can remain in the comminuted product. Improved methods of preparing micronized particles are needed to provide pharmaceutical formulations of poorly water soluble bioactive agents which can be readily prepared and which can improve the bioavailability of the poorly water soluble bioactive agent.